Cranial Radiotherapy Plus Chemoimmunotherapy in Untreated Driver-mutation Negative NSCLC With Active Brain Metastasis

Study Purpose

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, has a significant risk of brain metastasis (BM). Historically, the median overall survival for advanced NSCLC patients with BM was under six months with traditional chemotherapy. However, recent advancements with immune checkpoint inhibitors (ICIs) have shown promise, with some studies reporting improved intracranial objective response rates, progression-free survival, and overall survival when combined with chemotherapy. Despite these improvements, challenges remain, such as treatment resistance, recurrence, and the need for better therapeutic strategies. Local interventions like stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) have been crucial for treating BM, with SRT being particularly effective. The combination of immunotherapy and radiotherapy is emerging as a synergistic approach, with studies suggesting it may enhance local control and survival rates while maintaining safety. Guidelines recommend SRT for patients with limited BMs, and clinical data support the safety and efficacy of combining brain radiotherapy with immunotherapy. A meta-analysis and other studies have shown promising results with this combination, including local control rates and overall survival benefits, with manageable toxicities. However, there is still a need for more prospective clinical trials to verify the safety and efficacy of combining cranial radiotherapy with immunotherapy in NSCLC patients with BM, especially those without driver gene mutations. Therefore, we plan to conduct a phase 2 prospective study, focusing on combining brain radiotherapy with PD-1/PD-L1 inhibitors. Though most of the current studies excluded patients with active BM, we believe that these patients need more attention. In this trial, we focus on patients with active BM and treat them with PD-1/PD-L1 inhibitor, chemotherapy and SRT/WBRT.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Age ≥ 18 years; - KPS score ≥ 70; - Negative genetic testing for common driver genes including EGFR, ALK, ROS-1; - Pathologically confirmed non-small cell lung cancer; - Clinical stage IV (AJCC, 8th edition, 2017); - Diagnosed with brain metastasis at the time of diagnosis, with at least one lesion in the brain with a diameter greater than 5mm on thin-section brain MRI; - Active BMs that could not be controlled by symptomatic treatment, such as mannitol and dexamethasone.

- Complete baseline assessment of systemic lesions before treatment, including enhanced brain MRI; - Informed consent from the patient.

Exclusion Criteria:

- Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years); - Severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.; - Patients judged by the researcher as unsuitable for brain MRI or stereotactic brain radiotherapy; - EGFR, ALK, or ROS1 gene mutations; - Uncontrolled epilepsy, central nervous system disease, or history of mental disorders, judged by the researcher to potentially interfere with the signing of the informed consent form or affect patient compliance; - Symptomatic interstitial lung disease or active infection/non-infectious pneumonia; - Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation; - Patients with active infection, heart failure, myocardial infarction within 6 months, unstable angina, or unstable arrhythmia; - Other uncontrollable diseases or findings from physical examination or clinical experiments judged by the researcher to potentially interfere with the results or increase the risk of treatment complications for the patient; - Mixed with small cell lung cancer components; - Pregnant or lactating women; - Congenital or acquired immunodeficiency diseases including HIV, or history of organ transplantation, allogeneic stem cell transplantation; - Known HBV, HCV, active pulmonary tuberculosis infection; - Patients who have received tumor vaccines, or have been vaccinated with other vaccines within 4 weeks before starting treatment (Note: Seasonal influenza vaccines are usually inactivated vaccines and are allowed, while nasal preparations are usually attenuated live vaccines and are not allowed); - Concurrent use of other immunomodulators, chemotherapy drugs, drugs in other clinical studies, and long-term use of corticosteroid treatment are not eligible for inclusion; - Patients allergic or contraindicated to PD-1/PD-L1 inhibitors or chemotherapy drugs.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06501378
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Fudan University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	NSCLC Stage IV

Arms & Interventions

Arms

Experimental: active BM

Interventions

Drug: - PD-1/PD-L1 inhibitor plus chemotherapy

Active brain metastases patients will receive PD-L1/PD-1 inhibitors and chemotherapy.

Radiation: - SRT/WBRT

Active brain metastases (BM) patients will receive stereotactic radiotherapy (SRT) and whole brain radiation therapy (WBRT) according to their BM condition.

Contact a Trial Team

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International Sites

Fudan University Shanghai Cancer Center, Shanghai, China

Status

Recruiting

Address

Fudan University Shanghai Cancer Center

Shanghai, ,

Site Contact

Zhengfei Zhu, MD

[email protected]

+86-18017312901

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